lipopeptide

Lipopeptides are molecules that consist of a lipid tail covalently linked to a peptide, giving them amphiphilic properties. They are produced by bacteria and fungi, often as secondary metabolites, and can occur in cyclic or linear forms. Lipopeptides serve diverse roles, including functioning as biosurfactants, antibiotics, antifungals, and signaling molecules.

Structural features center on the attachment of a fatty acid lipid tail to a peptide moiety. This lipid head groups the molecule for membrane interaction, while the peptide portion provides specificity. Prominent examples from bacteria include cyclic lipopeptides such as surfactin, fengycin, and iturin produced by Bacillus species; clinically important cyclic lipopeptide antibiotics include daptomycin and the polymyxins. Fungal cyclic lipopeptides, such as echinocandins (caspofungin, micafungin, anidulafungin), are used as antifungals. The length and nature of the lipid tail, as well as peptide composition, influence spectrum and activity.

Biosynthesis is typically nonribosomal, carried out by large multi-enzyme complexes known as nonribosomal peptide synthetases (NRPS). These enzyme systems assemble the peptide portion modularly and incorporate nonproteinogenic amino acids, while acyltransferases attach lipid tails. Gene clusters coordinate production, tailoring, and export of the final lipopeptide.

Mechanisms of action vary but often involve interactions with membranes. Many lipopeptides disrupt or permeabilize lipid bilayers, causing pore formation or depolarization. Daptomycin requires calcium ions and targets Gram-positive membranes; polymyxins disrupt bacterial outer membranes by binding lipopolysaccharides; echinocandins inhibit fungal cell wall synthesis by blocking 1,3-beta-D-glucan synthase.

Applications span medicine, agriculture, and industry. Therapeutically, lipopeptides include antibiotics and antifungals; commercially they function as biosurfactants and biocontrol agents. Challenges include potential toxicity, antimicrobial resistance, and production costs.